This work has been supported by Spanish MINECO/FEDER SAF2017-86107-R to IV-N and MM., Peer reviewed

The raw data has been collected on each page, together with their statistical analysis for each figure., Sphingolipids are bioactive lipid components of cell membranes with important signal transduction functions in health and disease. Ceramide is the central building block for sphingolipid biosynthesis and is processed to form structurally and functionally distinct sphingolipids. Ceramide can be phosphorylated by ceramide kinase (CERK) to generate ceramide-1-phosphate, a cytoprotective signaling molecule that has been widely studied in multiple tissues and organs, including the developing otocyst. However, little is known about ceramide kinase regulation during inner ear development. Using chicken otocysts, we show that genes for CERK and other enzymes of ceramide metabolism are expressed during the early stages of inner ear development and that CERK is developmentally regulated at the otic vesicle stage. To explore its role in inner ear morphogenesis, we blocked CERK activity in organotypic cultures of otic vesicles with a specific inhibitor. Inhibition of CERK activity impaired proliferation and promoted apoptosis of epithelial otic progenitors. CERK inhibition also compromised neurogenesis of the acoustic-vestibular ganglion. Insulin-like growth factor-1 (IGF-1) is a key factor for proliferation, survival and differentiation in the chicken otocyst. CERK inhibition decreased IGF-1-induced AKT phosphorylation and blocked IGF-1-induced cell survival. Overall, our data suggest that CERK is activated as a central element in the network of anti-apoptotic pro-survival pathways elicited by IGF-1 during early inner ear development., This work was supported by the Spanish Ministerio de Economia y Competitividad, project FEDER/SAF2017-86107-R to IVN and MM., Peer reviewed

Multi Target and View FEDER/CM-B2017/BMD-3688; MINECO/FEDER SAF2017-86107-R., zip file containing 6 folders Bioanalyzer folder; Figure 1 folder [Figure1_qPCR.xlsx; Figure1_ABR.xlsx; Figure1_ Amplitudes_SPSS.pdf; Figure1_Audiogram_SPSS.pdf; Figure1_ Latencies_SPSS.pdf; Figure1_MyeP0 IHQ base.txt; Figure1_MyeP0 IHQ middle.txt; Figure1_MyeP0 IHQ quantification.xlsx]; Figure 2 folder [Figure2_CtBP2GluR2/3_ whole mount_quantification.xlsx; Figure2_Hair cells counts whole mount_quantification.xlsx; Figure2_Neurofilament number of fibers_quantification; Figure2_Neurofilament Intensity OHC_quantification.xlsx]; Figure 3 folder [Figure3_Western Blot_quantification analysis.xlsx; Exp0_p22phox Mb2 20170608_1327 Prec8sectif_AllLanes.pdf; Exp0_PI3K Mb2 20170608_1500 Prec8sectif_AllLanes.pdf; Exp1_p22phox_Mb4_20180222_1340_Prec2sec_tapandotif_AllLanes.pdf; Exp1_PI3K_Mb4_20180216_1446_Prec4sectif_AllLanes.pdf; Figure3_3NT IHQ quantification intensity; Figure3_Cyt C Oxidase IHF quantification intensity.xlsx; Figure3_qPCR Source Data.xlsx]; Figure 4 folder [Figure4_Western Blot_quantification analysis.xlsx; Figure4_Western Blot_ImageQuant; Figure4_TUNEL+ whole mount_quantification.xlsx]; Figure 5 folder [Figure5_qPCR .xlsx; Figure5_IBA1 IHF quantification]., Peer reviewed